The present invention relates to mass spectrometers and methods of mass spectrometry.
Ion guides comprising rf-only multipole rod sets such as quadrupoles, hexapoles and octopoles are well known.
Whitehouse and co-workers have disclosed in WO98/06481 and WO99/62101 an arrangement wherein a multipole rod set ion guide extends between two vacuum chambers. However, as will be appreciated by those skilled in the art, since each rod in a multipole rod set has a typical diameter of around 5 mm, and a space must be provided between opposed rods in order for there to be an ion guiding region, then the interchamber aperture when using such an arrangement is correspondingly very large (i.e.  greater than 15 mm in diameter) with a corresponding cross sectional area  greater than 150 mm2. Such large interchamber apertures drastically reduce the effectiveness of the vacuum pumps which are most effective when the interchamber orifice is as small as possible (i.e. only a few millimeters in diameter).
It is therefore desired to provide an improved interchamber ion guide.
According to a first aspect of the present invention, there is provided a mass spectrometer as claimed in claim 1.
Conventional arrangements typically provide two discrete multipole ion guides in adjacent vacuum chambers with a differential pumping aperture therebetween. Such an arrangement suffers from a disruption to the rf field near the end of a multipole rod set and other end effects. However, according to the preferred embodiment of the present invention, the ions do not leave the ion guide as they pass from one vacuum chamber to another. Accordingly, end effect problems are effectively eliminated thereby resulting in improved ion transmission.
An ion guide comprised of electrodes having apertures may take two main different forms. In a first form all the internal apertures of the electrodes are substantially the same size. Such an arrangement is known as an xe2x80x9cion tunnelxe2x80x9d. However, a second form referred to as an xe2x80x9cion funnelxe2x80x9d is known wherein the electrodes have internal apertures which become progressively smaller in size. Both forms are intended to fall within the scope of the present invention. The apertured electrodes in either case may comprise ring or annular electrodes. The inner circumference of the electrodes is preferably substantially circular. However, the outer circumference of the electrodes does not need to be circular and embodiments of the present invention are contemplated wherein the outer profile of the electrodes takes on other shapes.
The preferred embodiment of the present invention uses an ion tunnel ion guide and it has been found that an ion tunnel ion guide exhibits an approximately 25-75% improvement in ion transmission efficiency compared with a conventional multipole, e.g. hexapole, ion guide of comparable length. The reasons for this enhanced ion transmission efficiency are not fully understood, but it is thought that the ion tunnel may have a greater acceptance angle and a greater acceptance area than a comparable multipole rod set ion guide.
Accordingly, one advantage of the preferred embodiment is an improvement in ion transmission efficiency.
Although an ion tunnel ion guide is preferred, according to a less preferred embodiment, the inter-vacuum chamber ion guide may comprise an ion funnel. In order to act as an ion guide, a dc potential gradient is applied along the length of the ion funnel in order to urge ions through the progressively smaller internal apertures of the electrodes. The ion funnel is believed however to suffer from a narrow mass to charge ratio bandpass transmission efficiency. Such problems are not found when using an ion tunnel ion guide.
Various types of other ion optical devices are also known including multipole rod sets, Einzel lenses, segmented multipoles, short (solid) quadrupole pre/post filter lenses (xe2x80x9cstubbiesxe2x80x9d), 3D quadrupole ion traps comprising a central doughnut shaped electrode together with two concave end cap electrodes, and linear (2D) quadrupole ion traps comprising a multipole rod set with entrance and exit ring electrodes. However, such devices are not intended to fall within the scope of the present invention.
According to a particularly preferred feature of the present invention, one of the electrodes forming the ion guide may form or constitute a differential pumping aperture between two vacuum chambers. Such an arrangement is particularly advantageous since it allows the interchamber orifice to be much smaller than that which would be provided if a multipole rod set ion guide were used. A smaller interchamber orifice allows the vacuum pumps pumping each vacuum chamber to operate more efficiently.
The electrode forming the differential pumping aperture may either have an internal aperture of different size (e.g. smaller) than the other electrodes forming the ion guide or may have the same sized internal aperture. The electrode forming the differential pumping aperture and/or the other electrodes may have an internal diameter selected from the group comprising: (i) 0.5-1.5 mm; (ii) 1.5-2.5 mm; (iii) 2.5-3.5 mm; (iv) 3.5-4.5 mm; (v) 4.5-5.5 mm; (vi) 5.5-6.5 mm; (vii) 6.5-7.5 mm; (viii) 7.5-8.5 mm; (ix) 8.5-9.5 mm; (x) 9.5-10.5 mm; (xi) xe2x89xa610.0 mm; (xii) xe2x89xa69.0 mm; (xiii) xe2x89xa68.0 mm; (xiv) xe2x89xa67.0 mm; (xv) xe2x89xa66.0 mm; (xvi) xe2x89xa65.0 mm; (xvii) xe2x89xa64.0 mm; (xviii) xe2x89xa63.0 mm; (xix) xe2x89xa62.0 mm; (xx) xe2x89xa61.0 mm; (xxi) 0-2 mm; (xxii) 2-4 mm; (xxiii) 4-6 mm; (xxiv) 6-8 mm; and (xxv) 8-10 mm.
The differential pumping aperture may have an area selected from the group comprising: (i) xe2x89xa640 mm2; (ii) xe2x89xa635 mm2; (iii) xe2x89xa630 mm2; (iv) xe2x89xa625 mm2; (v) xe2x89xa620 mm2; (vi) xe2x89xa615 mm2; (vii) xe2x89xa610 mm2; and (viii) xe2x89xa65 mm2. The area of the differential pumping aperture may therefore be more than an order of magnitude smaller than the area of the differential pumping aperture inherent with using a multipole ion guide to extend between two vacuum regions.
The ion guide may comprise at least 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 or 200 electrodes. At least 90%, preferably 100% of the electrodes may be arranged and adapted to be maintained at substantially the same dc reference potential upon which an AC voltage is superimposed.
According to the preferred embodiment, when the ion guide extends between two vacuum chambers, the pressure in the upstream vacuum chamber may, preferably, be: (i) xe2x89xa70.5 mbar; (ii) xe2x89xa70.7 mbar; (iii) xe2x89xa71.0 mbar; (iv) xe2x89xa71.3 mbar; (v) xe2x89xa71.5 mbar; (vi) xe2x89xa72.0 mbar; (vii) xe2x89xa75.0 mbar; (viii) xe2x89xa710.0 mbar; (ix) 1-5 mbar; (x) 1-2 mbar; or (xi) 0.5-1.5 mbar. Preferably, the pressure is less than 30 mbar and further preferably less than 20 mbar. The pressure in the downstream vacuum chamber may, preferably, be: (i) 10xe2x88x923-10xe2x88x922 mbar; (ii) xe2x89xa72xc3x9710xe2x88x923 mbar; (iii) xe2x89xa75xc3x9710xe2x88x923 mbar; (iv) xe2x89xa610xe2x88x922 mbar; (v) 10xe2x88x923-5xc3x9710xe2x88x923 mbar; or (vi) 5xc3x9710xe2x88x923-10xe2x88x922 mbar.
At least a majority, preferably all, of the electrodes forming the ion guide may have apertures having internal diameters or dimensions: (i) xe2x89xa65.0 mm; (ii) xe2x89xa64.5 mm; (iii) xe2x89xa64.0 mm; (iv) xe2x89xa63.5 mm; (v) xe2x89xa63.0 mm; (vi) xe2x89xa62.5 mm; (vii) 3.0xc2x10.5 mm; (viii) xe2x89xa610.0 mm; (ix) xe2x89xa69.0 mm; (x) xe2x89xa68.0 mm; (xi) xe2x89xa67.0 mm; (xii) xe2x89xa66.0 mm; (xiii) 5.0xc2x10.5 mm; or (xiv) 4-6 mm.
The length of the ion guide may be: (i) xe2x89xa7100 mm; (ii) xe2x89xa7120 mm; (iii) xe2x89xa7150 mm; (iv) 130xc2x110 mm; (v) 100-150 mm; (vi) xe2x89xa6160 mm; (vii) xe2x89xa6180 mm; (viii) xe2x89xa6200 mm; (ix) 130-150 mm; (x) 120-180 mm; (xi) 120-140 mm; (xii) 130 mmxc2x15, 10, 15, 20, 25 or 30 mm; (xiii) 50-300 mm; (xiv) 150-300 mm; (xv) xe2x89xa750 mm; (xvi) 50-100 mm; (xvii) 60-90 mm; (xviii) xe2x89xa775 mm; (xix) 50-75 mm; (xx) 75-100 mm; (xxi) approx. 26 cm; (xxii) 24-28 cm; (xxiii) 20-30 cm; or (xxiv) xe2x89xa730 cm.
According to a preferred embodiment, the ion source is an atmospheric pressure ion source such as an Electrospray (xe2x80x9cESxe2x80x9d) ion source or an Atmospheric Pressure Chemical Ionisation (xe2x80x9cAPCIxe2x80x9d) ion source. According to an alternative embodiment, the ion source may be a Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source or an Inductively Coupled Plasma (xe2x80x9cICPxe2x80x9d) ion source. The MALDI ion source may be either an atmospheric source or a low vacuum source.
According to a preferred embodiment, the ion source is a continuous ion source.
The mass spectrometer preferably comprises either a time-of-flight mass analyser, preferably an orthogonal time of flight mass analyser, a quadrupole mass analyser or a quadrupole ion trap.
According to a second aspect of the present invention, there is provided a mass spectrometer as claimed in claim 21.
Preferably, an electrode of the ion guide forms a differential pumping aperture between the input and intermediate vacuum chambers.
Preferably, the mass spectrometer comprises means for supplying an AC-voltage to the electrodes. Preferably, an AC generator is provided which is connected to the electrodes in such a way that at any instant during an AC cycle of the output of the AC generator, adjacent ones of the electrodes forming the AC-only ion guide are supplied respectively with approximately equal positive and negative potentials relative to a reference potential.
In one embodiment the AC power supply may be an RF power supply. However, the present invention is not intended to be limited to RF frequencies. Furthermore, xe2x80x9cACxe2x80x9d is intended to mean simply that the waveform alternates and hence embodiments of the present invention are also contemplated wherein non-sinusoidal waveforms including square waves are supplied to the ion guide.
According to a third aspect of the present invention, there is provided a mass spectrometer as claimed in claim 24.
Preferably, at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 100 of the electrodes are disposed in one or both vacuum chambers.
According to a fourth aspect of the present invention, there is provided a mass spectrometer as claimed in claim 29.
According to a fifth aspect of the present invention, there is provided a mass spectrometer as claimed in claim 30.
Preferably, a differential pumping aperture between the vacuum chambers is formed by an electrode of the ion guide, the differential pumping aperture having an area xe2x89xa620 mm2, preferably xe2x89xa615 mm2, further preferably xe2x89xa610 mm.
According to a sixth aspect of the present invention, there is provided a mass spectrometer as claimed in claim 32.
According to a seventh aspect of the present invention, there is provided a mass spectrometer as claimed in claim 33.
According to a eighth aspect of the present invention, there is provided a mass spectrometer as claimed in claim 34.
According to this embodiment a substantially continuous ion tunnel ion guide may be provided which extends through two, three, four or more vacuum chambers. Also, instead of each vacuum chamber being separately pumped, a single split flow vacuum pump may preferably be used to pump each chamber.
According to a ninth aspect of the present invention, there is provided a method of mass spectrometry as claimed in claim 35.
According to a tenth aspect of the present invention, there is provided a method of mass spectrometry as claimed in claim 36.
According to an eleventh aspect of the present invention, there is provided a mass spectrometer as claimed in claim 37.